Affinage

FBXL13

F-box and leucine-rich repeat protein 13 · UniProt Q8NEE6

Length
735 aa
Mass
83.9 kDa
Annotated
2026-06-09
12 papers in source corpus 3 papers cited in narrative 3 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 3/3 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

FBXL13 is a centrosome-enriched F-box protein that serves as the substrate-recognition subunit of an SCF (SKP1-CUL1-F-box) E3 ubiquitin ligase, coupling substrate selection to proteasomal degradation in the control of centrosome biology (PMID:29348145). It directly targets CEP192 for degradation and associates with the centrosomal proteins Centrin-2, Centrin-3, and CEP152; induced FBXL13 expression lowers centrosomal γ-tubulin and disrupts microtubule arrays, whereas its depletion elevates CEP192 and γ-tubulin at centrosomes and impairs cell motility, establishing FBXL13 as a negative regulator of centrosomal microtubule nucleation capacity and migration (PMID:29348145). In a distinct context, FBXL13 (DRC6) is a component of the Nexin-Dynein Regulatory Complex (N-DRC) of sperm flagella, where its flagellar localization depends on TCTE1 (DRC5) (PMID:38650655); however, Fbxl13 knockout mice are fertile with normal axoneme ultrastructure, indicating it is dispensable for N-DRC assembly and male fertility under normal conditions (PMID:31961863).

Mechanistic history

Synthesis pass · year-by-year structured walk · 3 steps
  1. 2018 High

    Established FBXL13 as a functional SCF E3 ligase substrate receptor and identified CEP192 as its degradation target, defining how FBXL13 restrains centrosomal microtubule nucleation and cell motility.

    Evidence Co-IP, proteasomal degradation assays, and overexpression/knockdown with γ-tubulin and CEP192 quantification plus motility assays in cultured cells

    PMID:29348145

    Open questions at the time
    • Degron/recognition motif on CEP192 not mapped
    • Functional roles of Centrin-2/Centrin-3/CEP152 interactions not resolved
    • In vivo requirement for centrosomal function not tested in animals
  2. 2020 Medium

    Placed FBXL13 (DRC6) within the flagellar N-DRC and tested its physiological necessity, revealing it is dispensable for N-DRC assembly and male fertility in mice.

    Evidence Fbxl13 knockout mice with fertility assays and electron microscopy of axoneme ultrastructure

    PMID:31961863

    Open questions at the time
    • Negative phenotype leaves FBXL13's specific N-DRC role undefined
    • Possible redundancy or conditional requirement not addressed
    • Relationship between centrosomal SCF function and flagellar role unexplored
  3. 2024 Medium

    Resolved the dependency of FBXL13 flagellar targeting, showing TCTE1 is required to transport FBXL13 into the sperm flagellum.

    Evidence Immunofluorescence in situ staining of N-DRC proteins in WT versus Tcte1 KO mouse spermatozoa

    PMID:38650655

    Open questions at the time
    • Single-lab localization study without biochemical reconstitution
    • Mechanism of TCTE1-dependent transport not defined
    • Whether FBXL13 retains E3 ligase activity within the flagellum is unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • How FBXL13's two reported roles — SCF-mediated CEP192 degradation at the centrosome and structural participation in the flagellar N-DRC — relate mechanistically remains unresolved.
  • No structural model of FBXL13 or its SCF complex
  • Full substrate repertoire beyond CEP192 unknown
  • In vivo significance of centrosomal function in mammals untested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 1 GO:0140096 catalytic activity, acting on a protein 1
Localization
GO:0005929 cilium 2 GO:0005815 microtubule organizing center 1
Pathway
R-HSA-392499 Metabolism of proteins 1
Partners
CEP152CEP192CETN2CETN3DRC7EPS8L1TCTE1
Complex memberships
Nexin-Dynein Regulatory Complex (N-DRC)SCF (SKP1-CUL1-F-box) E3 ubiquitin ligase

Evidence

Reading pass · 3 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2018 FBXL13 functions as the substrate-recognition subunit of an SCF (SKP1-CUL1-F-box) E3 ubiquitin ligase complex, localizes to centrosomes, and directly targets CEP192 for proteasomal degradation. FBXL13 also interacts with centrosomal proteins Centrin-2, Centrin-3, and CEP152. Induced FBXL13 expression downregulates centrosomal γ-tubulin and disrupts centrosomal microtubule arrays; conversely, depletion of FBXL13 causes elevated CEP192 and γ-tubulin at centrosomes and defects in cell motility. Co-immunoprecipitation, proteasomal degradation assays, overexpression and knockdown with centrosomal marker quantification (γ-tubulin, CEP192), cell motility assays EMBO reports High 29348145
2020 In mice, FBXL13 (DRC6) is a component of the Nexin-Dynein Regulatory Complex (N-DRC) in sperm flagella, interacting with TCTE1 (DRC5) and DRC7. However, Fbxl13 knockout mice show no obvious phenotype, demonstrating that FBXL13 is dispensable for N-DRC assembly and male fertility in mice under normal conditions. Genetic knockout (Fbxl13 KO mice), fertility assays, electron microscopy of axoneme ultrastructure PLoS genetics Medium 31961863
2024 Immunofluorescence in situ staining in mouse spermatozoa confirmed FBXL13 (DRC6) protein localizes to the sperm flagellum as part of the N-DRC complex, co-localizing with TCTE1 (DRC5), DRC7, and EPS8L1 (DRC3). In Tcte1 knockout mice, FBXL13 protein fails to be transported to the sperm flagella, indicating FBXL13 flagellar localization depends on TCTE1. Immunofluorescence in situ staining of N-DRC proteins (Tcte1, Drc7, Fbxl13, Eps8l1) in mouse spermatozoa from WT and Tcte1 KO mice Human reproduction open Medium 38650655

Source papers

Stage 0 corpus · 12 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2005 Isolation and analysis of candidate myeloid tumor suppressor genes from a commonly deleted segment of 7q22. Genomics 41 15820312
2020 Nexin-Dynein regulatory complex component DRC7 but not FBXL13 is required for sperm flagellum formation and male fertility in mice. PLoS genetics 40 31961863
2016 Highly heterogeneous genomic landscape of uterine leiomyomas by whole exome sequencing and genome-wide arrays. Fertility and sterility 38 27889101
2018 FBXL13 directs the proteolysis of CEP192 to regulate centrosome homeostasis and cell migration. EMBO reports 26 29348145
2021 Identification of Serum Exosomal MicroRNA Expression Profiling in Menopausal Females with Osteoporosis by High-throughput Sequencing. Current medical science 24 33428145
2022 Genome-Wide Association Study and Genetic Correlation Scan Provide Insights into Its Genetic Architecture of Sleep Health Score in the UK Biobank Cohort. Nature and science of sleep 19 35023977
2014 Identifying genetic interactions associated with late-onset Alzheimer's disease. BioData mining 17 25649863
2017 A Genome-Wide Association Study and Complex Network Identify Four Core Hub Genes in Bipolar Disorder. International journal of molecular sciences 11 29257106
2015 Quantification of African cassava mosaic virus (ACMV) and East African cassava mosaic virus (EACMV-UG) in single and mixed infected Cassava (Manihot esculenta Crantz) using quantitative PCR. Journal of virological methods 4 26456453
2025 OTX2 expression contributes progression of gastric cancer in young adults. Scientific reports 1 40341176
2024 Effects of Tcte1 knockout on energy chain transportation and spermatogenesis: implications for male infertility. Human reproduction open 1 38650655
2025 Genome-wide genetic characterization and selection signatures in Anatolian Merino sheep. Archives animal breeding 0 42256732

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